title: Nitric oxide, atrial natriuretic peptide, and cyclic GMP inhibit the growth-promoting effects of norepinephrine in cardiac myocytes and fibroblasts.
abstract: This study tested the hypothesis that nitric oxide (NO) and atrial natriuretic peptide (ANP) can attenuate the effects of adrenergic agonists on the growth of cardiac myocytes and fibroblasts. In ventricular cells cultured from neonatal rat heart, ANP and the NO donor S-nitroso-N-acetyl-D,L-penicillamine (SNAP) caused concentration-dependent decreases in the norepinephrine (NE)-stimulated incorporation of [3H]leucine in myocytes and [3H]thymidine in fibroblasts. In myocytes, the NO synthase inhibitor NG-monomethyl-L-arginine potentiated NE-stimulated [3H]leucine incorporation. In both cell types, ANP and SNAP increased intracellular cGMP levels, and their growth-suppressing effects were mimicked by the cGMP analogue 8-bromo-cGMP. Furthermore, in myocytes, 8-bromo-cGMP attenuated the alpha1-adrenergic receptor-stimulated increases in c-fos. Likewise, ANP and 8-bromo-cGMP attenuated the alpha1-adrenergic receptor- stimulated increase in prepro-ANP mRNA and the alpha1-adrenergic receptor-stimulated decrease in sarcoplasmic reticulum calcium ATPase mRNA. The L-type Ca2+ channel blockers verapamil and nifedipine inhibited NE-stimulated incorporation of [3H]leucine in myocytes and [3H]thymidine in fibroblasts, and these effects were not additive with those of ANP, SNAP, or 8-bromo-cGMP. In myocytes, the Ca2+ channel agonist BAY K8644 caused an increase in [3H]leucine incorporation which was inhibited by ANP. These findings indicate that NO and ANP can attenuate the effects of NE on the growth of cardiac myocytes and fibroblasts, most likely by a cGMP-mediated inhibition of NE-stimulated Ca2+ influx.
authors.affiliation: Department of Medicine, Boston Medical Center, Boston, Massachusetts 02118, USA.
authors.forename: A
authors.initials: A
authors.lastname: Calderone
authors.forename: C M
authors.initials: CM
authors.lastname: Thaik
authors.forename: N
authors.initials: N
authors.lastname: Takahashi
authors.forename: D L
authors.initials: DL
authors.lastname: Chang
authors.forename: W S
authors.initials: WS
authors.lastname: Colucci
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D000252:Calcium-Transporting ATPases / Q000096:biosynthesis / Q000235:genetics; D002478:Cells, Cultured; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D006321:Heart / Q000187:drug effects; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D009638:Norepinephrine / Q000378:metabolism* / Q000494:pharmacology; D010396:Penicillamine / Q000031:analogs & derivatives / Q000494:pharmacology; D011498:Protein Precursors / Q000096:biosynthesis / Q000235:genetics; D011500:Protein Synthesis Inhibitors / Q000378:metabolism* / Q000494:pharmacology; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D026423:S-Nitroso-N-Acetylpenicillamine; D012519:Sarcoplasmic Reticulum / Q000201:enzymology; D013936:Thymidine / Q000493:pharmacokinetics; D014316:Tritium / Q000493:pharmacokinetics; D019323:omega-N-Methylarginine / Q000494:pharmacology
chemical_list: D000316:Adrenergic alpha-Agonists; D004791:Enzyme Inhibitors; D011498:Protein Precursors; D011500:Protein Synthesis Inhibitors; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D014316:Tritium; D019323:omega-N-Methylarginine; C016276:8-bromocyclic GMP; D009569:Nitric Oxide; D026423:S-Nitroso-N-Acetylpenicillamine; D009320:Atrial Natriuretic Factor; D019001:Nitric Oxide Synthase; D000252:Calcium-Transporting ATPases; D010396:Penicillamine; D006152:Cyclic GMP; D002118:Calcium; D013936:Thymidine; D009638:Norepinephrine